Neuroleptic treatment of schizophrenia is characterized by a delayed and often incomplete response to medication. We will characterize the metabolic adaptation of the brain to neuroleptic intervention for the purpose of identifying factors associated with therapeutic response. We will use Positron Emission Tomography (PET) and the deoxyglucose method to measure the immediate and long-term effects of neuroleptic treatment on regional glucose metabolism. Glucose utilization is the final common path for the bioenergetics of all neurochemical processes. Thus, regardless of the important details of neurotransmitter system activations, the pattern of regional energy utilization should reflect the adaptation of the brain to neuroleptic intervention. For these studies, we will measure regional glucose metabolism in four groups: never-medicated schizophrenics, previously medicated drug-responsive schizophrenics, previously medicated drug-unresponsive schizophrenics, and normal control subjects. The specific aims of the experiments are: (1) to measure the metabolic consequences of a single neuroleptic dose in never-medicated schizophrenics and normal controls; (2) to measure the long-term metabolic consequences of neuroleptic treatment in never-medicated schizophrenics; (3) to measure the relationship between clinical outcome, metabolic patterns, and plasma homovanillic acid concentration as a function of time in drug-responsive and unresponsive schizophrenics; and (4) to measure the relationship between metabolic patterns and clinical outcome in drug responsive schizophrenics maintained over time at a low plasma level of neuroleptic. By measuring metabolic response to neuroleptic treatment, we hope to provide a new approach to study the pathophysiology of schizophrenia. We expect that new insights, derived from these results, will enable us to develop better diagnosis and treatment of this disease.